University of Groningen
Response to letter to the editor
Berends, Annika M A; Kerstens, Michiel N; Lenders, Jacques W M; Timmers, Henri J L M
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Journal of Clinical Endocrinology and Metabolism
DOI:
10.1210/clinem/dgaa602
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Citation for published version (APA):
Berends, A. M. A., Kerstens, M. N., Lenders, J. W. M., & Timmers, H. J. L. M. (2020). Response to letter to
the editor: "Approach to the Patient: Perioperative Management of the Patient With Pheochromocytoma or
Sympathetic Paraganglioma". Journal of Clinical Endocrinology and Metabolism, 105(12), [602].
https://doi.org/10.1210/clinem/dgaa602
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The Journal of Clinical Endocrinology & Metabolism, 2020, Vol. 105, No. 12, e4980–e4981
doi:10.1210/clinem/dgaa602 Letter to the Editor Response
ISSN Print 0021-972X ISSN Online 1945-7197 Printed in USA
e4980
https://academic.oup.com/jcem© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society.
Letter to the Editor Response
Response to Letter to the Editor: “Approach to the
Patient: Perioperative Management of the Patient With
Pheochromocytoma or Sympathetic Paraganglioma”
Annika M.A. Berends,
1Michiel N. Kerstens,
1Jacques W.M. Lenders,
2,3and
Henri J.L.M. Timmers
21
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the
Netherlands;
2Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; and
3Department of Medicine III, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany
ORCiD number: 0000-0002-1208-5748 (H. J.L.M. Timmers).
Received: 19 August 2020; Accepted: 6 September 2020; First Published Online: 7 September 2020; Corrected and Typeset: 13 October 2020.
To the Editor,
We thank Dr Yu for his comments in response to our article. According to Dr Yu, we did not sufficiently address 2 misconceptions on perioperative management in pa-tients with a pheochromocytoma. He states that we sug-gested that control of hypertension is more important than prevention of cardiovascular complications, based on the order in which we mentioned these goals. These goals, however, were described in random order and we did not mean to imply that one was more important than the other. Fluctuations in blood pressure and heart rate are nevertheless common in pheochromocytoma, may have deleterious effects per se, and are amenable to medical management. We do agree with Dr Yu that normotension does not preclude the occurrence of cardiovascular com-plications, an important message to which we have also brought attention.
In response to the alleged second misconception in our paper, Dr Yu suggests that the perioperative management should be more individualized. We agree that in general, any treatment should be tailored to the patient. In fact, when aiming at predefined perioperative hemodynamic tar-gets as we suggest, this automatically translates into an in-dividualized approach to the selection of drugs and doses.
Unfortunately, however, it is still largely unknown which specific preoperative factors reliably predict a person’s perioperative risk and the ensuing optimal treatment. His statement that preoperative echocardiography and 24-hour ambulatory blood pressure monitoring is unnecessary in patients harboring a small pheochromocytoma (ie, < 3 cm) who are physically fit implies that pheochromocytoma/ paraganglioma (PPGL)-related cardiovascular complica-tions are negligible under these circumstances. The notion of skipping these routine and noninvasive investigations is, however, not corroborated by the literature that was cited. For example, the study by Yu et al demonstrated that 17% of patients with a tumor smaller than 3 cm also devel-oped severe cardiovascular complications during unrelated procedures (1). In addition, in the series by Chen and col-leagues, a smaller tumor size was not accompanied with a lower rate of complications (2). Moreover, the clinical pic-ture of a PPGL-induced cardiomyopathy is often atypical. Only a minority presents with classical cardiac symptoms, and absence of cardiovascular risk factors or a young age does not protect against the development of this form of cardiomyopathy (3-5). Furthermore, the assumption that tumor size strongly influences the risk for cardiac compli-cations is not supported by a high level of evidence, as was SubSubBList2=SubBList=SubSubBList=SubBList SubBList2=BList=SubBList=BList HeadB/HeadA=HeadC=HeadB/HeadA=HeadC/HeadB HeadC/HeadB=HeadD=HeadC/HeadB=HeadC/HeadB HeadC=NList_dot_numeric1=HeadC=NList_dot_numeric HeadC/HeadB=NList_dot_numeric1=HeadC/HeadB=NList_dot_numeric HeadD=NList_dot_numeric1=HeadD=NList_dot_numeric HeadD/HeadC=NList_dot_numeric1=HeadD/HeadC=NList_dot_numeric SubBList2=NList_dot_numeric2=SubBList=NList_dot_numeric2 SubBList2=NList_dot_numeric=SubBList=NList_dot_numeric NList_dot_numeric2=HeadB=NList_dot_numeric=HeadB NList_dot_numeric3=HeadB=NList_dot_numeric=HeadB NList_dot_numeric2=SubBList1=NList_dot_numeric=SubBList1 NList_dot_numeric3=SubBList1=NList_dot_numeric=SubBList1 SubBList3=HeadD=SubBList_Before_Head=HeadD SubBList2=HeadD=SubBList_Before_Head=HeadD SubBList2=HeadB=SubBList=HeadB SubBList3=HeadB=SubBList=HeadB HeadC=NList_dot_numeric1(2Digit)=HeadC=NList_dot_numeric(2Digit) HeadC/HeadB=NList_dot_numeric1(2Digit)=HeadC/HeadB=NList_dot_numeric(2Digit) HeadD=NList_dot_numeric1(2Digit)=HeadD=NList_dot_numeric(2Digit) HeadD/HeadC=NList_dot_numeric1(2Digit)=HeadD/HeadC=NList_dot_numeric(2Digit) SubBList2(2Digit)=NList_dot_numeric2(2Digit)=SubBList(2Digit)=NList_dot_numeric2(2Digit) SubBList2(2Digit)=NList_dot_numeric(2Digit)=SubBList(2Digit)=NList_dot_numeric(2Digit) NList_dot_numeric2(2Digit)=HeadB=NList_dot_numeric(2Digit)=HeadB NList_dot_numeric3(2Digit)=HeadB=NList_dot_numeric(2Digit)=HeadB NList_dot_numeric2(2Digit)=SubBList1(2Digit)=NList_dot_numeric(2Digit)=SubBList1(2Digit) NList_dot_numeric3(2Digit)=SubBList1(2Digit)=NList_dot_numeric(2Digit)=SubBList1(2Digit) SubBList3(2Digit)=HeadD=SubBList(2Digit)=HeadD SubBList2(2Digit)=HeadD=SubBList(2Digit)=HeadD SubBList2(2Digit)=HeadB=SubBList(2Digit)=HeadB SubBList3(2Digit)=HeadB=SubBList(2Digit)=HeadB Extract3=BList3=Extract1=BList3 BList3=Extract3=BList3=Extract3_0
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The Journal of Clinical Endocrinology & Metabolism, 2020, Vol. 105, No. 12
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also shown in the review by Shen and Yu (6). Of relevance,preoperative demonstration of abnormalities on electro-cardiogram or echocardiography does predict an increased risk for cardiac complications (6).
In conclusion, a small PPGL size or the absence of symp-toms does not reliably predict a low perioperative risk. We do agree that the controversy with respect to the clin-ical value of presurgclin-ical treatment with α-adrenoreceptor blockers in modern-day medicine could be resolved only by a well-designed placebo-controlled trial. Until then, we recommend following the Endocrine Society’s guideline that all patients with a PPGL, regardless of blood pres-sure and tumor size, should undergo preoperative evalu-ation of cardiac function and blood pressure and receive presurgical treatment with α-adrenoreceptor blockers (7).
Additional Information
Correspondence and Reprint Requests: Henri J.L.M. Timmers,
MD, PhD, Radboud University Medical Center Nijmegen, De-partment of Internal Medicine, Section of Endocrinology, Geert Grooteplein Zuid 10, 6525 GA Nijmegen, P.O. Box 9101, 6500 HB,
the Netherlands. E-mail: Henri.Timmers@radboudumc.nl.
Disclosure Summary: The authors have nothing to disclose.
References
1. Yu R, Pitts A, Wei M. Small pheochromocytomas: signifi-cance, diagnosis, and outcome. J Clin Hypertens (Greenwich). 2012;14(5):307-315.
2. Chen Y, Chomsky-Higgins K, Nwaogu I, et al. Trends in adrenal surgery—the changing nature of tumors and patients. J Surg
Res. 2019;236:129-133.
3. Yu R, Nissen NN, Bannykh SI. Cardiac complications as initial manifestation of pheochromocytoma: frequency, outcome, and predictors. Endocr Pract. 2012;18(4):483-492.
4. Zhang R, Gupta D, Albert SG. Pheochromocytoma as a revers-ible cause of cardiomyopathy: analysis and review of the litera-ture. Int J Cardiol. 2017;249:319-323.
5. Y-Hassan S, Falhammar H. Pheochromocytoma- and paraganglioma-triggered Takotsubo syndrome. Endocrine. 2019;65(3):483-493.
6. Shen J, Yu R. Perioperative management of pheochromocytoma: the heart of the issue. Minerva Endocrinol. 2013;38(1):77-93. 7. Lenders JW, Duh QY, Eisenhofer G, et al; Endocrine Society.
Pheochromocytoma and paraganglioma: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2014;99(6):1915-1942.